Altered ultrasonic vocalizations and impaired social behaviors in a mouse model of copy number variation in the neuropeptide receptor VIPR2 gene

Abstract

Results of several large-scale genetic studies demonstrated that microduplications at 7q36.3, containing VIPR2 gene, represent risk factors for schizophrenia and autism spectrum disorder (ASD). VIPR2 encodes the VPAC2 receptor that binds two homologous neuropeptides, VIP and PACAP. To address how increased VIPR2 dosage might predispose to psychiatric disorders, we have developed a bacterial artificial chromosome (BAC) transgenic (Tg) mouse model of VIPR2 copy number variation. Here we investigated neonatal ultrasonic vocalizations (USVs), an early communicative signal of mother-pup interaction, and social behaviors in adults of VIPR2-BAC Tg mice. VIPR2 mRNA expression in the prefrontal cortex and hippocampus of VIPR2-BAC Tg mice was significantly increased compared to wild-type littermates. Toal and mean durations of USVs of VIPR2-BAC Tg pups at postnatal day 7 were significantly longer than those of wild-type pups. Additionally, qualitative analysis of USVs revealed that VIPR2-BAC Tg mice showed a low proportion of “short” calls. In adulthood, VIPR2-BAC Tg mice exhibited impaired social behaviors in the reciprocal social interaction test. These results suggest that increased VIPR2 disrupts social communication development and this might lead to form some features of ASD or schizophrenia.